Ancrod improves survival in murine systemic lupus erythematosus.
The effect of ancrod, a defibrinating agent, on murine lupus glomerulonephritis in the male BXSB mouse was studied to determine the relationship between macrophage procoagulant activity (PCA), fibrin deposition and glomerulonephritis. Marked renal disease and fibrin deposition were noted by three months of age in control mice, whereas little or no disease was seen in ancrod treated mice until five months of age. Similar high titers of anti-DNA antibodies and renal deposition of IgG were seen in both groups of mice. PCA rose with age in both ancrod treated and untreated mice, although it was significantly higher in control animals than in the ancrod treated group. Furthermore, ancrod therapy resulted in a decrease in plasma PCA inducing activity (PIF) and a decrease in the effectiveness of PIF to induce PCA in peritoneal macrophages in vitro. No mortality was observed in the 20 ancrod treated mice, whereas 10 of 20 control animals died. We conclude that defibrination with ancrod delays the development of renal fibrin deposition and glomerulonephritis and improves survival in BXSB mice. This was associated with a decrease in plasma PCA inducing activity and with an inhibitory effect on PCA induction. These results suggest that PCA contributes to injury in murine lupus glomerulonephritis by promoting fibrin deposition.
Cole
E H
EH
Department of Medicine, University of Toronto, Ontario, Canada.
Glynn
M F
MF
Laskin
C A
CA
Sweet
J
J
Mason
N
N
Levy
G A
GA
D000721:Ancrod / Q000627:therapeutic use*; D000818:Animals; D001779:Blood Coagulation Factors / Q000187:drug effects; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D008181:Lupus Nephritis / Q000097:blood / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D013997:Time Factors
D001779:Blood Coagulation Factors; C045072:macrophage procoagulant activity; D005337:Fibrin; D005340:Fibrinogen; D000721:Ancrod